This project is part (Project 2) of the research consortium project Long Acting Acceptable Microbicides: Novel Delivery, Activity and Pharmacodynamics. It will evaluate new gel and ring materials for delivery of microbicides to the vaginal lumen and epithelium. New in vitro and in vivo assays, and mathematical models, of gel distribution, drug delivery and HIV neutralization will be developed. Together with current techniques operational in our laboratory, this diversified set of performance analysis assays will provide feedback to Projects 1 and 3 of the research consortium. The in vitro assays and mathematical models will relate gel and ring properties and potency of active microbicidal ingredients to the extent that semen borne HIV is neutralized before it migrates into epithelium and initiates the transmission process. Current and new in vivo imaging techniques will map the coating of human vaginal epithelium by microbicide gels. This information will help enable Project 1 develop new gels and rings with properties optimized for good vaginal distribution and drug delivery. Interactions with Project 3 will link biophysical properties of the gels and rings to measures of their perception and acceptability by women. Together, Projects 1, 2 and 3 will create new microbicide gels and rings with properties co-optimized to provide good biological activity against HIV transmission and good behavioral acceptability by women.